Cup is essential foroskarmRNA translational repression during earlyDrosophilaoogenesis

Abstract

ABSTRACTThe proper timing of mRNA translation is crucial across many biological systems for processes such as intercellular communication, body pattern formation, and morphogenesis. The mainD. melanogasterposterior determinant,oskar, is maternally transcribed, but only translated when properly localized at the oocyte’s posterior cortex. Bruno 1 and Cup are two effector proteins known to participate in multiple aspects ofoskarmRNA regulation. Current model describes a mechanism in which Bruno 1 is necessary for Cup’s recruitment tooskarmRNA, and Bruno 1 is indispensable for its translational repression. Here, we reveal that the Bruno 1-Cup interaction, as well as their interdependent influence on each other’s mRNA and protein expression, lead to preciseoskarmRNA regulation during early oogenesis. We show that these factors stably associate with theoskarmRNAin vivo, but surprisingly, Bruno 1’s stable association withoskarmRNA depends on Cup, while Bruno 1 is not necessary for Cup association tooskarmRNA. During early oogenesis, Cup, not Bruno 1, is the essential factor foroskarmRNA repression. Cup is a crucial P-body member that maintains proper P-body morphology during oogenesis, as well as it is necessary foroskarmRNA’s association with P-bodies, thus driving the translational repression and stability ofoskarmRNA. Our experimental results collectively suggest a regulatory mechanism where a feedback loop between Bruno 1 and Cup coordinatesoskarmRNA regulation in the egg chamber allowing for proper development to occur.